The assessment of lung mechanical function in small animals, particularly mice, is essential for many investigations into the pathophysiology of pulmonary disease. The forced oscillation technique applied in anesthetized tracheostomized animals provides the most accurate and specific assessment of lung function but is highly invasive. Unrestrained plethysmography in conscious animals provides a parameter called PenH, but this quantity is actually a reflection of the control of breathing and not lung mechanics. Thus, there is currently no completely noninvasive method available for determining lung function in small animals, despite the continued erroneous use of PenH in this regard. However, our research has shown that unrestrained plethysmography would provide a valid means for following changes in lung mechanical function if it could be coupled to independent measurements of changes in lung volume. Accordingly, the goal of our proposal is to extend unrestrained plethysmography by coupling it to an innovative method of measuring changes in lung volume using orthogonal video images of the thorax. Our studies to date have established the feasibility of this approach, which will form the basis of unrestrained video-assisted plethysmography (UVAP). We will develop and validate UVAP in three specific aims: SPECIFIC AIM 1: To develop unrestrained video-assisted plethysmography (UVAP) by incorporating an orthogonal video system for tracking changes in lung volume into a heated and humidified body plethysmograph. SPECIFIC AIM 2: To define how mouse preparation and maintenance determine accuracy of lung function measurement by UVAP. SPECIFIC AIM 3: To validate UVAP by using it to track changes in airway resistance in mouse models of lung disease. The results of this work will provide researchers with a tool for noninvasively following changes in airway resistance in mice, which should prove invaluable for the rapid screening of large numbers of animals, and for the non-destructive testing of valuable mouse models of lung disease.